Limited data are available on the responses to vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant in the Chinese population. This study aimed to investigate whether vaccination could alter the disease course of SARS-CoV-2 Omicron variant.A retrospective cohort included 142 patients who had no or mild symptoms and were admitted to our department for centralized isolation after being locally infected with SARS-CoV-2 Omicron variant from March 4 to 30, 2022, in Shanghai, China.Of the 142 subjects with the mean age of 43.1 years, 53.5% were male and 90.8% had been vaccinated before the infection. Comparing the vaccinated with the unvaccinated patients, there was no difference in patient characteristics, but patients with vaccination had shorter time to target cycle threshold value (TtCT) . There was no difference in TtCT between heterogeneous and homologous vaccination. Of subjects with homologous vaccination, 43.1% were vaccinated with CoronaVac (Sinovac Life Science), 47.2% with Sinopharm BBIBP-CorV, 4.9% with Sinopharm WIBP, 3.3% with CanSinoBio, and 1.6% with Zhifei Longcom. No difference in TtCT was observed among different vaccines. Comparing two-dose primary vaccination with three-dose booster vaccination, we found no difference in TtCT either.Vaccination is associated with shorter TtCT in patients with SARS-CoV-2 Omicron variant. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for more than 2 years. It threatens our health and lives and seriously disrupts the daily life. The SARS-CoV-2 keeps mutating, resulting in a number of variants . The OmiAlthough the SARS-CoV-2 vaccines currently have been reported to reduce the incidence of severe cases after infection , it is uThis is a retrospective cohort study including 142 patients who were locally infected with SARS-CoV-2 Omicron variant on March 2022 in Shanghai, China. They had no or mild symptoms and were admitted to our department for centralized isolation. At admission, the demographic and health information of all patients were collected and saved in the electronic medical records. The SARS-CoV-2 vaccination history of each patient was inquired in detail, including vaccination date, names of vaccine manufacturer, and times of vaccination. This study was conducted in accordance with the Declaration of Helsinki, and its ethical approval was obtained from the Ethics Committee of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. All participants were informed of the nature and objectives of the study. Informed consent was obtained from each enrolled subject.After nasopharyngeal swab samples were collected, they were shifted to the laboratories immediately and the PCR tests started within 2 h. Real-time fluorescent reverse transcriptase–PCR was used to detect different viral RNA sequences of SARS-CoV-2, including open reading frame (ORF1ab), nucleocapsid (N), and envelope (E) genes. All PCR tests were performed in laboratories of Shanghai Public Health Clinical Center Affiliated to Fudan University, using the SARS-CoV-2 RNA detection kit  with the SLAN Real-time PCR system following the manufacturer’s instructions. In brief, the total volume of the reaction mixture was 25 μl, and it contained 5 μl of RNA template. The reaction conditions were as follows: reverse transcription at 50°C for 10 min; cDNA pre-denaturation at 97°C for 1 min; denaturation at 97°C for 5 s (45 cycles); then annealing and elongation (with fluorescence monitoring) at 58°C for 30 s; and a final step at 25°C for 10 min. The CT value of each target gene was reported.The patient received the first nucleic acid amplification test (NAAT) on the second day after admission and the second NAAT on the seventh day after admission. If the CT value was ≥35, then the patient continued to receive the next NAAT in the next day. If the CT value was <35, then the patient received NAAT every other day. Two weeks after admission, NAAT was performed every day.The latest Diagnosis and Treatment Plan of SARS-CoV-2  was released by the National Health Commission of the People’s Republic of China on March 2022, and the discharge criteria for mild cases were revised as the CT values ≥ 35 of N gene and ORF gene tested by NAAT  for two consecutive samples with over 24-h interval. In the world, it is generally judged as negative when the CT value exceeds 35. In China, it is judged as negative when the CT value exceeds 40, so as to powerfully reduce the risk of SARS-CoV-2 transmission. The CT value of the new scheme was reduced from 40 to 35, which is limited to the criteria for being out of quarantine and discharge for mild cases after treatment. The adjustment of CT value for discharge is of great significance to improve the allocation of medical resources in China but does not mean that the positive diagnostic criteria for SARS-CoV-2 have changed. TtCT was defined as the duration from the date when the infection of SARS-CoV-2 was first confirmed by NAAT to the date when the patient got two consecutive CT values greater than 35 for both N gene and ORF gene of SARS-CoV-2 with an interval of more than 24 h. Homologous vaccination is defined as multiple injections with the same vaccines and heterogeneous vaccination is defined as multiple injections with different kinds of vaccines.2 at baseline or having a history of chronic renal failure.Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or current antihypertensive therapy. Diabetes mellitus was defined as having a previous diagnosis of diabetes mellitus, receiving oral hypoglycemic agents or insulin treatment, or having a fasting plasma glucose ≥126 mg/dl (7.0 mmol/L) or a hemoglobin A1c level ≥6.5%. The history of coronary heart disease (CHD) was made primarily according to clinical symptoms of angina pectoris, ECG manifestations of myocardial ischemia, and coronary stenosis showed by contrast-enhanced coronary computed tomography angiography or percutaneous coronary angiography. Stroke was defined as a history of cerebral thromboembolism or bleeding manifested by brain computed tomography or magnetic resonance imaging. Renal dysfunction was defined as the estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 mFor numerical variables, the mean (standard deviation) was used for statistical description, and the t-test or ANOVA was performed for inter-group comparison. Categorical data were presented as absolute value and percentage, and they were compared between groups with the chi-square test. All statistical analyses were performed with SPSS 13.0. Two-tailed P-value of less than 0.05 was considered of statistical significance.The 142 patients were locally infected with SARS-CoV-2 Omicron variant from March 4 to 30, 2022, in Shanghai, China. Sixty-nine (53.5%) of them were male, and the mean age was 43.1 years . The 90.8% of them had been vaccinated before infection. Comparing the vaccinated with the unvaccinated patients, we found no difference in patient characteristics Table 1.Compared with patients who did not receive vaccination, patients with vaccination had shorter TtCT  Figure 1Overall, we have identified 129 patients with SARS-CoV-2 infection after vaccination, of which 69 (53.5%) of them were male and the mean age was 42.9 years  Table 1.For subjects with homologous vaccination, they all were vaccinated with inactivated COVID-19 vaccines produced by the five Chinese manufacturers, such as Sinovac Life Science, Beijing Bio-Institute of Biological Products (BBIBP), Wuhan Institute of Biological Products (WIBP), CanSinoBio, and Zhifei Longcom. Patients vaccinated with CoronaVac (Sinovac Life Science) accounted for 43.1%, Sinopharm BBIBP-CorV for 47.2%, Sinopharm WIBP for 4.9%, CanSinoBio for 3.3%, and Zhifei Longcom for 1.6%  Vaccination is associated with shorter TtCT in patients with SARS-CoV-2 Omicron variant; 2) inactivated vaccines produced by different manufacturers in China have similar effects on TtCT; and 3) compared with the two-dose primary vaccination, the three-dose booster vaccination does not appear to reduce TtCT.Currently, vaccination has been verified to be the most effective way to prevent SARS-CoV-2, irrespective of the mRNA or the inactivated vaccines . AlthougA meta-analysis of different vaccines at phase 3 indicated that mRNA vaccines conferred a lesser risk of SARS-COV-2 infection and showed more relevance to serious adverse events than viral vector and inactivated vaccines . A higheThe inactivated SARS-CoV-2 vaccines have been widely used in a two-dose schedule . A thirdIn conclusion, vaccination is associated with shorter TtCT in patients with SARS-CoV-2 Omicron variant. It indicates that the inactivated vaccines keep working effectively against SARS-CoV-2 Omicron variant in Chinese population.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. The patients/participants provided their written informed consent to participate in this study.Conceptualization: YW; methodology: YW and JW; formal analysis: YW; investigation: YW, JW, FS, SZ, YL, XT, and PZ; writing: YW. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The STarT-MSK-Tool is an adaptation of the well established STarT-Back-Tool, used to risk-stratify patients with a wider range of musculoskeletal presentations.G) and to establish its reliability and validity.To formally translate and cross-culturally adapt the Keele STarT-MSK risk stratification tool into German  using correlations, ROC-curves and regression models.G-Tool against the OMPQ-Tool of rs = 0.74 . The ability of the tool [comparison OMPQ] to predict 6-month pain and disability was acceptable with AUC = 0.77  [OMPQ = 0.74] and 0.76  [OMPQ = 0.72] respectively. However, the explained variance (linear/logistic regression) for predicting 6-month pain (21% [OMPQ = 17%]/logistic = 29%) and disability (linear = 20%:[OMPQ = 19%]/logistic = 26%), whilst being comparable to the existing OMPQ reference standard, fell short of the a priori target of ≥30%.The participants’ (n = 287) mean age was 47 (SD = 15.8) years, 51% were female, with 48.8% at low, 43.6% at medium, and 7.7% at high risk. With ICC = 0.75  test-retest-reliability was good. Construct validity was good with correlations for the STarT-MSKThe German version of the STarT-MSK-Tool is a valid instrument for use across multiple musculoskeletal conditions and is availabe for use in clinical practice. Comparison with the OMPQ suggests it is a good alternative. Subgrouping for Targeted Treatment). It allocates patients to one of three prognostic sub-groups  in which they receive a risk-matched treatment [Musculoskeletal (MSK) disorders comprising pain in the region of the lower back, the neck, or osteoarthritis affecting the joints of the upper or lower extremities are among the leading causes of disability. These complaints often have a chronic course and their burden on individuals and society is large –3. Due treatment –10. Thisreatment , 11. Intreatment , 13. Onereatment .Through a programme of research the STarT-Back-Tool has therefore been adapted and validated to produce the Keele STarT-MSK risk stratification tool (STarT-MSK) for use in a broader musculskeletal patient population . This apA translated version of the original STarT-MSK could support German physiotherapists, physicians or other health professionals to be able to provide risk-based stratified care for musculoskeletal disorders , 18. RisG). Moreover, we aimed to investigate its test-retest reliability, construct validity discriminative ability, predictive ability and floor or ceiling effects.The objective of this study was, to formally translate and cross-culturally adapt the STarT-MSK-Tool into German (German version: STarT-MSKA cohort study including a retest (t1) and a half-year follow-up (t2) in addition to the intitial assessment (t0) was conducted. Patients were recruited from physiotherapy clinics (n = 7). The inclusion criteria were patients 18 years or older with acute, subacute or chronic complaints in the region of the lumbar spine, the hip or knee, the shoulder or the neck. The exclusion criteria were those with a known or suspected tumor, an acute inflammatory condition, recent musculoskeletal-related surgery (last six months) or trauma (last 3 months). German language skills had to be sufficient to complete the study questionnaires and participants had to provide written consent and their email and telephone details for follow-up purposes.Initial data (t0) was collected electronically in the clinics via SoSci Survey . The invEthical approval was granted by the Ethics Committee of Trier University of Applied Sciences, Computer Science/Therapeutic Sciences (registration ID: 01–2019). All patients gave their written informed consent for participation before enrollment in the clinics.G. There are two versions of the STarT-MSK-Tool: (1st) a self-report version which was used in this study and (2nd) a clinical interview version. A copy of the instrument can be requested here: www.keele.ac.uk/startmsk.The instrument validated in this study is the STarT-MSKThe translation and cross-cultural adaptation was done according to internationally accepted guidelines and with permission for translation from the developers of the original version . The trawww.keele.ac.uk/startmsk.To check for acceptability and comprehension a pre-test was carried out with 10 patients from a German physiotherapy clinic. A Think-Aloud method was utilized, while the tool was completed . MoreoveDIS) [DIS) [To test for construct validity several reference instruments were added. Based on a formative model, both, the STarT-MSK like the OMPQ assess the risk for future pain and disability, using a set of items of known biopsychosocial risk factors , 35, 36.DIS) , Roland DIS)  or WesteS) [DIS) . Pain inS) [DIS) , 42.The STarT-MSK comprises of 10 items. The first item is an 11-point numeric pain rating scale. The other nine items have a dichotomous response option: yes/no. To calculate a sum-score, the items are recoded . The final score is calculated by summarizing the point for all 10 items, with a possible total score ranging from 0 to 12. Based on cut-off points established for the original version, a total score of ≤4 points indicates low risk, a total score between 5–8 points medium risk, and ≥9 points high risk for persisting pain disability .DIS-score was calculated by summarizing the item values, then divided by the number of items resulting in a range from 0 to 10 points [DIS-score was calculated by summarizing the item values, then divided by the number of valid items, with maximally one non-valid item accepted. This also resulted in a score ranging from 0 to 10 points [To determine the OMPQ score the sum of the five subscale means was computed resulting in a possible range from 0 to 50 points . The RMD0 points . The SPA0 points .Descriptive statistics were calculated to characterize the study population and each subgroup. The baseline characteristics of the study participants are provided to allow interpretability of the study sample. Moreover, numbers on recruitment rate, drop-outs and missing data were described.test-retest reliability the intraclass correlation coefficient ) was used. An ICC above 0.50 was considered acceptable [To investigate the ceptable . Additioconstruct validity the STarT-MSKG was related to the OMPQ. Spearman correlations were calculated for the time point t0. A priori a positive correlation was expected, with higher scores meaning worse prognosis on both instruments. The magnitude of the reported correlation coefficient was evaluated with a correlation of 0.1–0.3 considered to be small, >0.3–0.5 to be moderate, and greater than 0.5 to be large [At least a moderate correlation of greater than 0.4 was considered sufficient. Additionally, to visually represent the correlation of the instruments, box and whisker plot graphs were be presented using the OMPQ-score for each subgroup defined by the STarT-MSKG score. Next to the relation with the OMPQ, coefficients (Spearman) for the correlation with the reference instruments for disability were calculated across the pain sites  curves with areas under the curves (AUC) and 95% confidence interval (CI) were computed [DIS [DIS [DIS ≥ 2.1 [DIS ≥ 4.1 [To assess STarT-MSKcomputed . The curcomputed , NDI [37ted [DIS , SPADIDIDIS [DIS ). MoreovDIS [DIS , NDI ≥ 1DIS [DIS , WOMACDIIS ≥ 2.1 , SPADIDIIS ≥ 4.1 .At least acceptable discrimination for disability was expected.Adjectives that can be used to describe AUC-values have been proposed by Hosmer and Lemeshow with an AUC = 0.5 suggesting ‘no discrimination’, 0.7 to < 0.8 considered ‘acceptable discrimination’, 0.8 to 0.9 considered ‘excellent discrimination’ and >0.9 considered ‘outstanding discrimination’ . At leaspredictive ability the t0 score of the STarT-MSKGwas used as the predictor variable in univariate linear regression. It was aimed to explain a proportion of at least 30% of variance in the outcome (disability and pain). For comparison purposes the variance explained by the OMPQ was also calculated. Additionally, logistic regression analyses were performed. For dichotomization of disability the thresholds given above were used (see discriminative ability), for pain intensity the median was used (with 2.7 at t0 and 4.3 at t2 this fitted well with thresholds described in the literature [2-statistics (adjusted/ Nagelkerke) explaining the variance were evaluated. To test the calibration of the logistic prediction models, Spiegelhalter’s z test was used [To analyse the terature , 53). Thwas used , 55.G predicting dichotomised t2-outcomes (dichotomisation see discriminative ability). Moreover, to enable comparison, AUCs were calculated for OMPQ predicting dichotomised t2-outcomes.Next to regression analyses and in parallel to the procedure described for discriminative ability, areas under the curves (AUC) with 95% confidence intervals (CI) were calculated for STarT-MSKTerwee et al. suggested a sample size of 50 patients for construct validity and reliability . TherefoAs significance level alpha = 5% was set. Analyses were performed using SPSS version 27.0 and R language and environment for statistical computing, version 4.0.0 .Consent for participation was given by 287 patients. The mean age was 47 (SD 15.8) years, and 51% were female, with overall 48.8% at low, 43.6% at medium and 7.7% at high risk. . Non-conThere were 122 patients with lower back complaints, 65 with neck, 40 with shoulder and 60 with hip/knee complaints. Thirty-six patients (12.5%) previously received surgery in the region of their complaints. Additional details on the characteristics of the study population are given in The median time interval between t0 and t1 was 7 (IQR = 8) days and between t0 and t2 181 (IQR = 11) days. The follow-up questionnaires sent to the patients at t1 and t2 were returned by 261 (91%) and 246 (86%) of the participants, respectively. Non-responders at t1 on average were 6.5 years younger than responders, with a large confidence interval  and were less often female . Non-responders at t2 on average were 6.6 years younger than responders, with a confidence interval not including zero  and were less often female .G was 0.75  and therefore, is ‘good’. For individual items the median κ was 0.58 (range 0.42 (item 9) to 0.72 (item 7 and 10)) (The ICC (t0 to t1) for the STarT-MSKand 10)) .G-Tool against the OMPQ-Tool was rs = 0.74 . A visual presentation of the correlation is given in G-Tool against the disability measures consistently was lower, ranging from rs = 0.44 to rs = 0.71 , indicating ‘acceptable’ discrimination. The AUC for pain was 0.83 , indicating ‘good’ discrimination  for pain at 6 months and 20% (variance explained by OMPQ 19%) for combined disability as shown by adjusted R2. The explained variance therefore fell short of the 30% aimed for, both for predicting pain and disability.The univariate logistic regression models, comparable were statistically significant, with both p < 0.001, resulting in an amount of variance explained by the STarT-MSKG of 29% for pain at 6 months and 26% for combined disability as shown by Nagelkerke’s R2. With z = -0.01 for disability and z = 0.07 for pain, Spiegelhalter’s z was non-significant .For the univariate G ability to predict pain-cases at follow-up was 0.77 . The AUC for disability was 0.76 , indicating ‘acceptable’ prediction  was used . The goo2>30%. The number of 30% was estimated based on results from the development study, being unpublished at the time [G together with covariables could be analysed for example in multiple regression analyses. Comparably, for the German version of the STarT-Back-Tool, adding a one item-variable capturing global health status and the baseline score of the outcome (disability) successfully increased the variance explained to ≥45% [Predictive properties checked by ROC-Analyses resulted in acceptable AUCs that were higher than those of the OMPQ, although with extensively overlapping CI. The calculated, logistic and linear models with pain or disability outcomes explained from 20% to 29% of the variance in outcome, but did not exceed the pre-specified target of Rthe time . The achthe time . In futu to ≥45% . Moreove to ≥45% . In the  to ≥45% . CalculaG, it would be worthwhile to develop a study design specifically aiming at improving prediction.The treatment was not influenced by the researchers in the presented study, thus, it can be assumed that the content will have influenced the outcome at follow-up and the variance explained by the regression analyses. An alternative would have been to standardize the procedures, but such a shift from an observational to an experimental design would have led to costs exceeding the available resources for this project. On the other hand, to withhold therapy would have been unethical. Considering the other positive properties established for reliability and validity of the STarT-MSKAll predictive ROC at least resulted in acceptable AUC. The cut-offs used to differ between cases and non-cases were derived from the literature –50. NoneG is related to that of the STarT-Back-Tool. While the area of application of STarT-Back-Tool is limited to low back pain [G is its appropriability for patients with a variety of musculoskeletal complaints. In practice, such a possibility for generic use makes clinical processes easier with one instrument fitting for a broader group of patients. The administrative burden can be reduced, since often patients present with complaints at several sites simultaneously [The development of the STarT-MSKack pain , a strenaneously , 60. Moraneously , 62.G strengthens its use for this purpose. Since practitioners have mixed ideas about how to best make use of prognostic tools [Another strength of the STarT-MSK is that matched treatments were compiled and instruments assisting clinicians in decision-making are under development , 28, 63.ic tools , 67, strReference for the development of the STarT-MSK at Keele (UK) was the STarT-Back-Tool , 18. ThrNext to the German version multiple other translations were done including the Dutch, French, Hebrew and Norwegian versions which were validated. However, three of those studies were conducted with smaller sample-sizes and only one with a design enabling determination of the instrument’s predictive ability , 19, 21.The low amount of dropout in this study is an area of strength. It is substantially lower than the benchmark set by the Cochrane Back and Neck Group for long term follow-up . This inConcerning the sample size, in the literature minimal numbers of 50 to 100 participants are required for validation , 71. In The German version of the STarT-MSK-Tool is a valid instrument for use across multiple musculoskeletal conditions and is availabe for use in clinical practice. It fulfils the fundamental requirements for an assessment instrument having shown good test-retest-reliability, face, construct validity and predictive validity when analysing ROC-Curves. The instrument explains a considerable amount of variance in six month pain and disability scores. However, whilst the prognostic abilities are comparable to those of the existing reference standard (OMPQ), as the variance was lower than the target set a priori, it is recommended that future research should seek to raise the predictive abilities of this tool further.S1 FigG total score; RMDQ: Roland Morris Disability Questionnaire; NDI: Neck Disability Index; SPADI: Shoulder Pain and Disability Index, subscale disability; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index, subscale disability; t0: initial.Disability-scores versus STarT-MSK(TIF)Click here for additional data file.S2 FigG total score; RMDQ: Roland Morris Disability Questionnaire; NDI: Neck Disability Index; SPADI: Shoulder Pain and Disability Index, subscale disability; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index, subscale disability; t2: follow-up.Disability-scores versus STarT-MSK(TIF)Click here for additional data file.


The 1-year survival rates were 100% in Group A, 60% in Group B, and 43% in Group C. Patients in Group C showed the shortest overall survival among the three groups. The vascular-poor pattern on late-phase CH-EUS had the highest sensitivity, specificity, and accuracy for aggressive PanNENs among the patterns analyzed on CH-EUS and CECT . CH-EUS is useful for the diagnosis of and predicting the prognosis of PanNENs.The purpose of this study is to clarify the associations between the enhancement patterns on contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and the aggressiveness and prognosis of pancreatic neuroendocrine neoplasms (PanNENs). Patients who underwent CH-EUS and were pathologically diagnosed with PanNEN were included in this study. Patients were divided into three groups according to contrast-enhancement patterns on early-phase and late-phase imaging: “Group A”, vascular rich in both phases; “Group B”, vascular rich and vascular poor in early and late phases, respectively; “Group C”, vascular poor in both phases. Of 39 patients, 25 were assigned to Group A, 7 to Group B, and 7 to Group C. The median overall survival was not reached in Groups A and B and was 335 days in Group C ( Pancreatic neuroendocrine neoplasm (PanNEN) has a frequency of 0.32–0.43 per 100,000 persons per year and accounts for about 1–2% of all pancreatic neoplasm cases . The Ki-Although EUS is the usual radiological method for diagnosing pancreatic neoplasms, it is often difficult to distinguish pancreatic ductal adenocarcinoma from PanNEN using only fundamental B-mode EUS . In thisThis retrospective single-center cohort study was approved by the institutional review boards of the Wakayama Medical University. We informed the study subjects of the outline of this study on the website or bulletin board of our hospital and provided an opportunity to decline participation.The cohort consisted of consecutive patients diagnosed with PanNENs between October 2012 and March 2022 at Wakayama Medical University, Japan. Patients were included in the study if they (1) were 20 years of age or older and underwent CH-EUS and (2) were diagnosed with PanNEN using pathological diagnosis. All data were abstracted from medical records from which personal identifiers were redacted. According to previous reports, aggressive PanNENs include Grade 3 (G3) tumors, neuroendocrine carcinoma (NEC), mixed neuroendocrine and non-neuroendocrine neoplasia (MiNEN), or any grade of tumor that had metastasis at diagnosis or during follow-up ,11. In rCH-EUS was performed by endosonographers with experience of more than 500 EUS procedures. All patients underwent CH-EUS using a GF-UCT260 linear echoendoscope  connected to a Prosound α-10, ARIETTA 850 , or EU-ME2  ultrasound scanning system. Sonazoid  at 15 μL/kg was used as the ultrasound contrast agent.The ultrasound (US) contrast agent contains gas-filled microbubbles that form a lipophilic shell with a lipid monolayer. These microbubbles resonate in response to pressure waves when irradiated with US. On the other hand, the harmonic components responsible for the reflected signal from biological tissue are called “tissue harmonics”, and the reflected signal from resonant contrast agent microbubbles contains multiple insertion frequencies called harmonics ,14,15. HFirst, the pancreatic mass lesion was detected on fundamental B-mode EUS, and then the viewing screen was changed to dual-screen mode with fundamental B-mode and CH-EUS mode imaging. The transmitting frequency was 5 MHz, and the MI value was 0.2–0.4. The focus point was set to the bottom of the EUS screen. The penetration of the CH-EUS ultrasound beam is inferior to that of fundamental B-mode imaging, and therefore the EUS should be positioned as close as possible to the target lesion before performing CH-EUS. Sonazoid was injected intravenously, followed by an intravenous injection of 10 mL of physiological saline.In a pancreatic lesion, the signal from the contrast agent appears 10–15 s after injection and reaches a peak approximately 20 s later. The examination of a lesion lasted a minimum of 90 s after the Sonazoid injection. The contrast phase was defined as the arterial phase (early) of 10–30 s , followed by the venous phase (late) of 30–90 s . Solid pancreatic lesions were classified into four patterns according to the intensity of their enhancement on CH-EUS: nonenhancement, hypoenhancement, isoenhancement, and hyperenhancement. Then, the solid pancreatic lesions were classified into two groups based on the status of the intratumoral vessels: vascular-rich appearance (hyper- or isoenhancement) and vascular-poor appearance (non- or hypoenhancement). In addition, to evaluate lesions according to the differences in their intratumoral vascularity pattern on CH-EUS, patients were classified into the following three groups according to the vascular patterns on early- and late-phase imaging. PanNENs that had a vascular-rich appearance in both phases were defined as Group A, PanNENs that had a vascular-rich appearance on early-phase imaging and a vascular-poor appearance on late-phase imaging were classified as Group B, and PanNENs that had a vascular-poor appearance in both phases were classified as Group C . None ofAll EUS images were interpreted by two endoscopists (T.T. and Y.S.) who were blinded to the clinical findings. If there was a difference in the evaluation between the two readers, the radiologists reviewed the data together until a consensus was reached.A 64-channel multidetector CT scanner  with a section thickness of 1 mm was used for CECT. After an unenhanced scan, patients were administered nonionic contrast material (1.7 mL/kg body weight) with an iodine concentration of 350 mg/mL  for a fixed duration of 25 s. The scan delay for the arterial and portal venous phases was 20 and 48 s, respectively, after aortic enhancement exceeded 150 HU compared with the baseline value. Pancreatic lesions were evaluated for attenuation relative to that of the surrounding pancreatic parenchyma and were classified as hypo-, iso-, or hyperdense according to the methods of a previous study . The solPanNENs were diagnosed pathologically using hematoxylin and eosin staining and an immunohistochemical analysis of chromogranin A, synaptophysin, and/or CD56. The specimens were obtained using surgical resection or EUS-FNA. The Ki-67 proliferation index was also evaluated from the surgical specimen or EUS-FNA sampling. In the case of both a surgical specimen and an EUS-FNA sample, the surgical specimen was used. The grading of the tumors was based on the WHO 2017 classification with three groups: G1, Ki-67 < 2%; G2, Ki-67 = 3–20%; and G3, Ki-67 > 20%.The primary outcomes were associations between the contrast-enhancement patterns of PanNENs on CH-EUS imaging and tumor aggressiveness, with tumor size, grade classification, and overall survival being analyzed.Secondary outcomes were the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CH-EUS imaging for the diagnosis of aggressive PanNENs. A further outcome is a comparison of the diagnostic values of CH-EUS and CECT for aggressive PanNENs. A subgroup analysis was performed to reveal the characteristic contrast-enhancement patterns of aggressive PanNENs of the G1 or G2 classification.t-test. Prognostic ability was analyzed using the Kaplan–Meier method, and surviving cases were censored. The log-rank test was used to compare survival curves. McNemar’s test was used to compare the diagnostic accuracy of CH-EUS and CECT for progressive PanNEN.Diagnostic values including diagnostic sensitivity, specificity, PPV, NPV, and accuracy were calculated. Among the demographic and clinical characteristics, categorical variables were analyzed using the Chi-squared test or Fisher’s exact test, while continuous variables were compared using the Wilcoxon rank-sum test or Student’s p values < 0.05 were considered to indicate statistical significance [Kappa values were calculated to assess interobserver variability in each phase and for each assessment of intratumor vascularity on CH-EUS, and 95% confidence intervals (CIs) were estimated using the jack-knife method. Kappa values were interpreted as follows: 0.00–0.20: poor agreement; 0.21–0.40: fair agreement; 0.41–0.60: moderate agreement; 0.61–0.80: substantial agreement; 0.81–1.00: almost perfect agreement. Statistical analyses were performed using JMP (Version Pro 13.0) and EzR (version 3.4.1) software. For all analyses, The patient characteristics are summarized in The evaluations were classified into three groups according to the vascularity in the early and late phases of CH-EUS as follows: Group A = 25 patients, Group B = 7 patients, and Group C = 7 patients . Kappa vp = 0.004, 0.029, 0.011, 0.001, and <0.001, respectively).The patient characteristics of the three groups are summarized in p ≤ 0.001). The median overall survival was not reached in Groups A and B and was 335 days in Group C  ,13.The present study classifies PanNEN CH-EUS enhancement patterns into three types. In the Kaplan–Meier curves of overall survival, the patients in Group C had the shortest overall survival. The 1-year survival rate in this group was only 43%, whereas it was 60% in Group B. With respect to 1-year survival, the early phase of CH-EUS was useful for predicting the prognosis for aggressive PanNEN. The 1-year survival rate of Group C was as poor as that reported for pancreatic adenocarcinoma. The highest proportion of patients with G3 tumors or NEC was found in Group C. Takada et al. reported that G3/NEC shows weak contrast enhancement in the early-stage phase and that this weak contrast enhancement quickly declines . We suggCH-EUS is also a good way to evaluate the malignancy of PanNENs before surgery. The pathological evaluation of PanNENs using EUS-FNA may not always be accurate because of heterogeneity within the tumor. Therefore, treatment should be considered for PanNEN with a hypoenhancement area, even if the pathological diagnosis by EUS-FNA results in a grade of G1. If a hypoenhancement area appears within a PanNEN on follow-up CH-EUS imaging, it would be better to consider treatment for the PanNEN. It may be better to determine the treatment strategy for PanNEN with the consideration of both CH-EUS imaging and pathological evaluation using EUS-FNA.The present study has several limitations. This is a single-center retrospective study, and the number of aggressive PanNENs is small. In 25 of 39 cases, the final diagnosis was obtained with EUS-FNA, and it was reported that for PanNENs, the agreement between grading by EUS-FNA and that by surgical specimen is approximately 84% . AnotherIn conclusion, CH-EUS is useful for evaluating tumor aggressiveness and predicting the prognosis of PanNENs. Late-phase CH-EUS is useful for diagnosing aggressive PanNENs; on the other hand, early-phase CH-EUS is useful for predicting the prognosis of aggressive PanNEN. Aggressive therapeutic intervention should be considered for PanNENs that are vascular poor on CH-EUS, even for those with a tumor size of less than 20 mm and classified as Grade 1.


FMD protocols demonstrated similar good reproducibility. Leg occlusion was deemed more uncomfortable than arm occlusion; thigh occlusion was less tolerated than forearm and calf occlusion. FA-FMD with calf occlusion was lower than BA-FMD . Multivariate linear regression analysis indicated that age (−0.4%/decade) was a significant independent predictor of FA-FMD . The age-dependent decline in FMD did not significantly differ between FA and BA (interaction agexlocationp = 0.388). In older participants, 40% of baseline FA wall shear stress (WSS) values were <5 dyne/cm2, which is regarded as pro-atherogenic. In conclusion, endothelial function declines similarly with age in the FA and the BA in healthy adults. The age-dependent FA enlargement results in a critical decrease in WSS that may explain part of the age-dependent predisposition for PAD.Femoral artery (FA) endothelial function is a promising biomarker of lower extremity vascular health for peripheral artery disease (PAD) prevention and treatment; however, the impact of age on FA endothelial function has not been reported in healthy adults. Therefore, we evaluated the reproducibility and acceptability of flow-mediated dilation (FMD) in the FA and brachial artery (BA) ( The burden of lower extremity peripheral artery disease (PAD) is growing globally . The pren = 10). In the second study, we performed reproducibility measurements of BA- and FA-FMD  in healthy middle-aged people on 2 different days (n = 10). Finally, we performed cross-sectional measurements of FA  and BA-FMD in healthy non-smoking participants over a wide age range (n = 50). We performed three studies. We first compared the reproducibility and acceptability of BA-FMD with two different FA-FMD protocols using thigh and calf occlusion in healthy young participants on the same day .n = 10 reproducibility and n = 53 cross-section studies, respectively) were recruited consecutively for the three studies at the University of Surrey (January–May 2021) and measurements were performed at the Clinical Investigations Unit. Three subjects were removed from the cross-sectional study as they were smokers. All participants were self-reported apparently healthy adults with a BMI of 20–30 kg/m2. Exclusion criteria were clinical signs or symptoms of manifest cardiovascular disease (coronary artery disease (CAD)), PAD, cerebrovascular disease), diabetes mellitus, ankle brachial pressure index (ABPI) <0.9 or >1.4, heart rhythm other than sinus rhythm, symptoms of acute infection, and active vasoactive medication. When asked, none of the participants reported a past medical history of chronic disease, including autoimmune or chronic inflammatory disease.Seventy-three individuals (2 × Reproducibility and acceptability study same day (Study 1): We measured BA-FMD and FA-FMD with a 5-min distal occlusion  in the following sequence: FA-FMD (thigh), BA-FMD (forearm), FA-FMD (thigh), BA-FMD (forearm), FA-FMD . There was at least a 30-min interval between measurements on the same limb to allow recovery. To assess the feasibility and reproducibility of the different measurements, after explaining the procedure and before the commencement of measurements, we asked the participants to rate the expected discomfort based on a visual analogue scale for qualitative pain assessment from 0 (no discomfort) to 10 (most severe discomfort). Immediately after the first FMD measurement at each location, the participants rated the actual discomfort they experienced using the same scale. Finally, to assess acceptability, participants were asked if the discomfort was severe enough to prevent them from participating in future studies.Reproducibility FA-FMD calf occlusion (Study 2): To assess the reproducibility of calf occlusion, we measured BA-FMD and FA-FMD in the morning on two different days under fasting conditions.Cross-sectional study (Study 3): To assess the age-dependence of FA-FMD  and compare it with BA-FMD, we performed FMD measurements on the FA and the BA. We chose calf occlusion over thigh occlusion for FA-FMD measurement as thigh occlusion was not well tolerated by study participants. Together with FMD measurements, blood flow was assessed. In addition, we measured blood pressure with a cuff on the upper arm. The perfusion pressure of the legs was measured on the ankle arteries with a cuff placed around the lower leg following a standard protocol [protocol , allowinmaximum − diameterbaseline)/diameterbaseline * 100. Lower limb and forearm blood flow rates were calculated as π * mean radius 2 * mean velocity at baseline and peak immediately after reperfusion. The ratio of peak and baseline limb blood flow rate was used to calculate flow reserve. Wall shear stress was calculated as 8 * m * mean flow velocity/mean diameter, where blood viscosity (m) was assumed to be constant at 0.035 dyne*s/cm2 [FMD was measured in the right common femoral artery first (FA-FMD) then in the right brachial artery (BA-FMD) using 5-min distal occlusion with a fitted cuff in each case and ultrasound  in combination with a digital video frame grabber and a semi-automated analysis system . All measurements were conducted in the morning after an overnight fast. To assess FA-FMD, depending on the study (see above), the cuffs were either placed around the mid-thigh proximal to the knee (FA-FMD thigh occlusion) or calf just distal to the knee joint . For BA-FMD the cuff was placed around the proximal forearm (BA-FMD). Briefly, the FA or BA, respectively, was scanned above the femur head, or proximal to the elbow longitudinally, to obtain a clear anterior and posterior vessel wall-lumen interface. In ultrasound duplex mode, the Doppler spectrum showing blood flow velocity over time was visualised in parallel with the B-mode scan. After optimization of the settings, a video clip of 10 s duration was recorded for baseline pre-occlusion arterial diameter analysis. Then an appropriately sized blood pressure cuff around the thigh, proximal calf or forearm was inflated to 200 mmHg for 5 min. Starting shortly before deflation of the cuff, the recording of a 2-min video of the continuous duplex scan was started [ne*s/cm2 . Shear rOffice blood pressure and pulse wave velocity were measured using a sphygmomanometer device  at the upper right arm in a supine position after 10 min of supine rest in a quiet room with the arm resting at heart level. Three blood pressure measurements were taken. The first reading was discarded and the remaining two were used to calculate an average which was used for further analyses . ABPI waThe baseline characteristics of the study population are expressed as mean values ± standard deviation (SD). Reproducibility was expressed as the average deviations (AD) and standard deviations of individual differences in FMD measurements on two occasions. AD was calculated as the group mean of individual differences between repeated measurements (second measurement minus first measurement). Differences between FA and BA measurements were compared with repeated measurements ANOVA and paired sample t-tests. Expected and experienced pain VAS data were treated as ordinal scale non-parametric data and compared using the Wilcoxon test. Correlations were Pearson’s correlations. Multivariate linear regression analyses were performed to identify significant independent predictors of BA-FMD and FA-FMD (dependent variables). Analyses were computed with SPSS 28 . Based on previous BA FMD studies, we expected a correlation coefficient (Pearson’s) between age and FMD of −0.4 . With a p = 0.486 (paired t-test)). The average deviation between the two BA-FMD measurements was −0.1% with a standard deviation of 0.6% (See p = 0.776). The average deviation between both FA-FMD (thigh) measurements was −0.1% with a standard deviation of 0.9%. Whereas BA-FMD and FA-FMD (thigh occlusion) did not significantly differ (BA-FMD: 6.2 ± 1.5% vs FA-FMD (thigh): 6.2 ± 1.6%, p = 0.746), FA-FMD with calf occlusion (5.2 ± 1.1%) was significantly lower than BA-FMD (p = 0.008), and FA-FMD with thigh occlusion .The characteristics of study participants are shown in p = 0.004 vs. expected) for BA, whereas 4/10 indicated moderate discomfort for FA calf  with FA thigh being least well tolerated with 7/10 rating their discomfort as moderate . None of the participants stated the discomfort was severe enough to prevent them from participating in future trials.In terms of acceptability, 4/10 anticipated minor and 6/10 moderate discomfort before the measurements (median 4 range 3–6) B. Post-mp = 0.221). The average deviation of both BA-FMD measurements was −0.3% with a standard deviation of 0.8%. The mean FA-FMD  of the first measurement was 5.2 ± 0.8% and of the second was 5.1 ± 0.1% (p = 0.742). The average deviation of both FA-FMD measurements with calf occlusion was −0.1% with a standard deviation of 0.6%. Again, the FA-FMD values were significantly lower than BA-FMD : 5.1 ± 0.9%, p = 0.036).As thigh occlusion was less well tolerated and participants of Study 1 were by chance younger than people receiving FA-FMD in a clinical setting, we performed a second study to evaluate the reproducibility of FA-FMD  as compared to BA-FMD in slightly older individuals on two different days  0.5 ± 1.1%). In addition, the baseline diameter, mean flow velocity and flow rate were significantly higher in the FA as compared to the BA whereas the WSS and SR were significantly lower. At the onset of PORH, the flow rate was significantly higher, but mean flow velocity, WSS, SR and flow reserve were lower in the FA as compared to the BA.In apparently healthy individuals aged 22-76 years n = 50, , FA-FMD r = 0.61, p < 0.001). Both FA-FMD and BA-FMD correlated inversely with age and baseline diameter and positively with WSS  of the variability of FA-FMD. In this model, only age was a significant independent predictor of FA-FMD. According to the unstandardised coefficient B in this model, with every decade FA-FMD was lower by 0.36% (p < 0.001). Similar results were seen in terms of BA-FMD  with age, sex, and baseline diameter being independent predictors. According to the unstandardised coefficient B, with every decade and every 1 mm larger BA, BA-FMD was lower by 0.41% (p = 0.002) and 0.67% (p = 0.042), respectively and female sex had 0.92% higher BA FMD than male (p = 0.025). Repeated measurements ANCOVA confirmed that age was a significant determinant of FMD decrease (agep < 0.001) and it also indicated that the age-dependent decrease of FMD did not significantly differ between FA and BA . It further indicated that the age-dependent increases in baseline diameters  and decreases in baseline WSS  did not differ significantly between FA and BA. While the peak PORH WSS was not quite statistically significantly related to age, there was also no difference between the effect of age on BA and FA values .Multivariate linear regression analysis, including age, sex, BMI, baseline diameter and systolic blood pressure, explained 35% (adjusted 2 is regarded as pro-atherogenic [n = 50), 28% (n = 14) and 6% (n = 3) of participants had FA and BA baseline WSS values below 5 dyne/cm2. Of note, all participants with <5 dyne/cm2 were older than 40 years and among the participants older than 40 years (n = 35) the percentage of individuals presenting with WSS values below 5 dyne/cm2 was 40% (FA) and 9% (BA).As WSS below 5 dyne/cmerogenic , we evalThe key findings of the current studies are that FMD measurements can be performed reproducibly in the common FA using both thigh and calf occlusion with calf occlusion being better tolerated. The FA-FMD decrease inversely correlates with age to a similar degree as BA-FMD in healthy individuals. WSS is on average lower in the FA as compared to the BA and decreases to a critical level with age more frequently in the FA than the BA. We have recently published healthy BA-FMD values to be used as reference values for cardiovascular health assessment . Our cur2, which is accepted to be a proatherogenic condition [2. We cautiously speculate these people may be at increased risk of developing PAD and targeted interventions may be able to prevent this. Our data could be used as reference values allowing the identification of people at risk for PAD (susceptibility biomarker) and as an organ-specific biomarker of lower limb health to therapeutically target one component of the underlying cause of PAD: endothelial dysfunction (predictive or response biomarkers) . Our preondition ,21,22. IThe potential clinical relevance of the current data lies in the fact that the values can serve as starting healthy reference values to allow indicative classification of values measured in patients as normal or decreased. Decreased values may indicate that the person is at increased risk of developing PAD (susceptibility biomarker). The limb-specific effect of treatments, including management of standard modifiable cardiovascular risk factors (SMuRFs)  and noveSeveral limitations apply to the study, the results and the FMD method in general. In the current study, we did not determine lipids, glucose, and cardiovascular family history, and there is the possibility that some of the participants had dyslipidaemia, insulin resistance, or familial risk. Therefore, true healthy reference values may be slightly higher or have a smaller variation. Another limitation of the FMD method for both BA and FA in terms of wider clinical adoption of the techniques lies in the fact that it only captures one time point, is time consuming, and requires high-quality ultrasound equipment, analysis software, and trained staff to perform the measurements . WhetherIn healthy adults, endothelial function declines with age in the FA to a similar degree as in the BA. However, the age-dependent enlargement of the FA leads to a critical decrease in WSS that may explain part of the age-dependent predisposition for PAD. Taken together, the data provide a sufficiently strong proof-of-concept to warrant further studies in larger populations. Future studies would support generalisability of results, further characterise determinants of FA-FMD and validate FA-FMD as a limb-specific cardiovascular biomarker to either predict PAD development or limb prognosis. They would also enable establishing if an improvement in FA-FMD by interventions can predict prevention of PAD development or amputations.


In this study, we proposed a multi-atlas-based [18F]-FP-DTBZ PET image segmentation method for PD quantification assessment.A total of 99 subjects from Xuanwu Hospital of Capital Medical University were included in this study, and both brain PET and magnetic resonance (MR) scans were conducted. Data from 20 subjects were used to generate atlases, based on which a multi-atlas-based [18F]-FP-DTBZ PET segmentation method was developed especially for striatum and its subregions. The proposed method was compared with the template-based method through striatal subregion parcellation performance and the standard uptake value ratio (SUVR) quantification accuracy. Discriminant analysis between healthy controls (HCs) and PD patients was further performed.p < 0.001). The median and posterior putamen performed best in discriminating patients with PD from HCs.Segmentation results of the multi-atlas-based method showed better consistency than the template-based method with the ground truth, yielding a dice coefficient of 0.81 over 0.73 on the full striatum. The SUVRs calculated by the multi-atlas-based method had an average interclass correlation coefficient (ICC) of 0.953 with the standardized result, whereas the template-based method only reached 0.815. The SUVRs of HCs were generally higher than that of patients with PD and showed significant differences in all of the striatal subregions (all The proposed multi-atlas-based [18F]-FP-DTBZ PET image segmentation method achieved better performance than the template-based method, indicating great potential in improving accuracy and efficiency for PD diagnosis in clinical routine. Parkinson’s disease (PD) is one of the most common age-related neurodegenerative disorders . An incrTo quantify the PET images, the target-to-reference standard uptake value ratio (SUVR) is extensively used, by which the accuracy of identifying regions of interest (ROIs) directly affects the credibility of the quantification results . MagnetiIn this study, we proposed a multi-atlas-based [18F]-FP-DTBZ PET image segmentation method, which implements reliable MR-free ROI extraction for PET images. Comparisons between the multi-atlas-based, template-based method, and the gold standard were conducted on the segmentation and quantification level. Quantification results were further analyzed to reveal the most sensitive subregions in discriminating patients with PD. This would provide reliable information for PD diagnosis and facilitate efficient clinical workflow.A total of 2 datasets with 99 subjects recruited from the Xuanwu Hospital of Capital Medical University were included in this study. All subjects underwent a PET and a high-resolution MR scan of the brain. UI dataset with PET/MR (scanned by United Imaging uPMR790) includes 30 HCs and 38 PDs. GE dataset with PET/MR  includes 11 HCs and 20 PDs. The PDs were diagnosed according to the MDS clinical diagnostic criteria for PD . The stuMagnetic resonance imaging data acquisition was performed using a hybrid 3.0-T PET/MR scanner  with a 24-channel head/neck coil. A 3D T1-weighted imaging (T1WI) data were collected from all participants with the following parameters: TR/TE: 7.86/3.2 ms; flip angle: 10; FOV: 230 mm × 256 mm; voxel size: 0.5 mm × 0.5 mm × 0.67 mm. Scanning parameters of [18F]-FP-DTBZ PET imaging were as follows: field of view = 300 mm; voxel size = 1.17 mm × 1.17 mm × 1.4 mm. All patients with PD were scanned during their off-state condition (12 h after the last medication).Positron emission tomography/MRI examinations were performed on an integrated simultaneous Signa PET/MR scanner . The scan began 90 min following an intravenous bolus injection of around 222 MBq (6 mCi) of [18F]-FP-DTBZ and lasted for 15 min. The PET bed position included a simultaneous 18-s 2-point Dixon scan for MRI-based attenuation correction as well as additional diagnostic 3D T1 BRAVO MR images with scanning parameters as follows: TR = 7.9 ms; TE = 3.6 ms; acquisition matrix = 232 × 224; acquired spatial voxel resolution 1.00 mm × 1.00 mm × 1.00 mm with a data acquisition time of 4 min and 17 s. Scanning parameters of PET imaging were as follows: field of view = 25 cm; matrix size = 192 × 192; voxel size = 1.82 mm × 1.82 mm × 2.78 mm; 89 slices. Attenuation correction, scatter correction, random correction, and dead-time correction were performed as well.The multi-atlas-based [18F]-FP-DTBZ PET image segmentation and analysis method were developed by the procedure illustrated in 1)  . An MR tlgorithm . By applAfter that, the PET images were coregistered to the PET template using the non-linear registration method by ANTs. The transform matrix and normalization parameters generated by these two steps were also applied to the label images. A manual check on segmentation accuracy for each participant was performed by a senior neurologist with 7-year experience in nuclear image processing.Several image preprocessing methods were applied to the PET images in the template space, including skull stripping, partial volume effect correction, smoothing, and histogram specification. Each individual skull stripped PET image was corrected for partial volume effect by PETPVC, with kernel size = 6.0 mm × 6.0 mm × 6.0 mm, number of iterations = 10, number of deconvolution iterations = 10, alpha value = 1.5, stopping criterion = 0.01 . The VOIFinally, an atlas database including a PET template and 20 atlases was obtained to provide segmentation reference for target PET images. Each atlas contained a PET image in the template space with a corresponding label image and its global as well as local histogram-specified results.Target PET images in cohort UI were coregistered to the template space and followed a similar preprocessing procedure as PET atlases  for further evaluation. Mean square error (MSE) was applied to measure the similarity between target PET images and atlases. For each target, five best-matched atlases from the atlas database were selected by following two steps. In the first step, MSE between each atlas’ global-specified PET image and the target’s global-specified PET image was calculated. A total of 10 atlases with the least MSE values were selected as the candidates for the second step. In the second step, five best-matched atlases were selected based on MSE calculated between local-specified regions  on PET images.The segmentation results were produced by merging the label images of the best-matched atlases. The joint label fusion  was performed to fuse the obtained multiple labels of the PET image for each target participant . First, A detailed subregion segmentation criterion based on the topographic structural information was adopted to find prominent parts of the striatum for discriminating patients with PD from HCs. The putamen and the caudate were divided into anterior, median, and posterior parts, respectively. Using the median point of the whole putamen pixels under the coronal axis, a sagittal plane was established to separate the striatum into left and right parts. Then, the bilateral putamen and caudate were further segmented into three equal parts along the line determined by their front-end and back-end points under the sagittal axis. Finally, the striatum was segmented into seven subregions . Standardized uptake value ratios of all seven subregions of the striatum on each PET image were calculated by dividing the mean counts per voxel in the target subregions by the mean counts per voxel in the reference region (Cerebellum):The result of the MR-based method was applied as the ground truth. MR images for cohort UI subjects were segmented by Brain Label and coregistered to PET images. The subregion segmentation criterion was the same as mentioned before, and the final results were manually checked by the experienced neurologist.Dice coefficient was applied to measure the similarity of segmentation results between the multi-atlas-based method and the MR-based method . It is cwhere A and B are two different segmentation results, respectively, and |⋅| represents the number of voxels within the segmentation result. A larger dice coefficient means better overlap. For larger structures, values above 0.8 are usually accepted as successful results while for smaller structures, values greater than 0.7 are preferred .The two-way mixed effect interclass correlation coefficients (ICCs) were calculated to identify the consistency between the SUVRs obtained by the two segmentation methods . ICC is s denotes variance caused by differences between the segmentation methods and σs denotes variance caused by differences between the values in the segmentation results.where σt-test and effect size. The t-test was further applied to compare SUVRs between HCs and patients with PD. Additionally, p < 0.05 was determined significant in our statistical results.Statistical analysis of demographic details between groups was performed using a two-sample We compared the segmentation accuracy of the striatum subregions between the multi-atlas-based and template-based methods on cohort UI. As shown in The subregion SUVR values were calculated according to the segmentation results generated by the multi-atlas-based method and the MR-based method, respectively. The correlation of results obtained by these two analyses was calculated and visualized in p < 0.001). The SUVRs of the median putamen and posterior putamen in patients with PD could be separated clearly from HCs without any overlap between the two groups. The t-test demonstrated SUVR values to be significantly different in all of the subregions for HCs and patients with PD (p < 0.001). Reproducibility experiments were performed on cohort GE. The multi-atlas-based PET image segmentation method and the MR-based method were applied to extract the ROI subregions. The dice coefficient of the two methods reached 0.792 on the whole striatum and 0.816, 0.788, and 0.652 on the putamen, caudate, and nucleus accumbens, respectively. SUVR of all subregions calculated by the multi-atlas-based method and the MR-based method is compared in In this study, we proposed a multi-atlas-based PET segmentation method that achieved reliable segmentation performance in an MR-free situation. Analysis on [18F]-FP-DTBZ PET quantification showed great potential for our method in PD diagnosis. The current PET image analysis methods mainly include the manual method, MR-based method, and MR-free template-based method. Our multi-atlas-based method was fully automatic and did not rely on MR images. Thus, it was operator-independent and had great reproducibility with high processing efficiency. As compared to the template-based method, our proposed method used an atlas database rather than a single template, which provided a higher parcellation accuracy. In the previous studies, the PET template was usually generated from HCs or adapted from existing results such as Montreal Neurological Institute (MNI) standard space, and target PET images were coregistered to the PET template directly . Given tOur method further segmented the striatum into seven subregions. The putamen and the caudate were divided into three parts, respectively. Our study showed that the reduction of VMAT2 integrity among patients with PD varies in different parts of the striatum. The improvement in the segmentation method helped to further distinguish patients with PD from HCs. Analysis of SUVR showed that all subregions of patients with PD exhibited different levels of lower VMAT2 densities than HCs, suggesting presynaptic nigrostriatal dysfunction in PD . The mosThe multi-atlas-based method also showed potential in processing datasets from other institutions and was expected to be applicable to other PET modalities . ReproduSeveral limitations in this study should be mentioned. First, a large number of subjects, as well as samples from other imaging centers for further validation, are warranted. Due to the limited sample size, our current atlas database only included 20 cases. Although a significant segmentation performance improvement has been achieved, more atlases were expected to provide better segmentation accuracy since more PET distribution patterns might be included. Second, our subregion segmentation criterion was restricted to topographic structural information. Through significant difference has been found in some of the subregions, the combination of structural connectivity and functional information might provide more insights into dopamine function and contribute to better subdivision , 2021b. In this study, a multi-atlas-based [18F]-FP-DTBZ PET image segmentation method was proposed for PD quantification and showed better performance than the template-based method. The application analysis in patients with PD suggests that the proposed method has potential value for improving the accuracy and efficiency of PD diagnostic in clinical routine.tma@hit.edu.cn.The datasets presented in this article are not readily available because it is for institutional use only. Requests to access the datasets should be directed to TM, The studies involving human participants were reviewed and approved by the Institutional Review Board of Xuanwu Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.TM conceived and supervised the project. HQ and TS helped the data acquisition. YP, SL, YZ, and CY analyzed the data. YP drafted the manuscript. YZ created the figures. CY and HL revised the manuscript. SL, PC, and JL provided the insight on clinical aspects. TM, JL, and PC gave final approval to the manuscript. All authors read and approved the final manuscript.HL was employed by Mindsgo Life Science Shenzhen Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Human T-lymphotropic viruses 1 and 2 (HTLV-1/2) have a worldwide distribution. HTLV-1 has been associated with several diseases, including an aggressive malignant disease known as adult T-cell leukemia/lymphoma and a chronic inflammatory neurological disease called HTLV-1-associated myelopathy, while HTLV-2 has not been definitively associated with diseases. HTLV-2 is most prevalent in specific groups such as injecting drug users and the indigenous population. In Brazil, most studies about HTLV in indigenous are carried out in indigenous communities from the north of the country. Mato Grosso do Sul (MS), Central Brazil, has the second-largest indigenous population in Brazil. However, there is no available data about HTLV infection in this group. We conducted the first investigation of HTLV-1/2 infection prevalence in the indigenous population from Jaguapiru and Bororó villages in Dourados City, MS, to provide the prevalence and molecular characterization of HTLV. For that, a total of 1875 indigenous participated in the study. All the serum samples were screened by an enzyme-linked immunosorbent assay commercial kit for the presence of anti-HTLV-1/2 antibodies. Positive samples were confirmed by HTLV-1/2 Western Blot assay. The HTLV-1 5’LTR region was detected by nested PCR amplification and sequenced by Sanger. Most of the study population declared belonging to Guarani-Kaiowá ethnicity (69.18%), 872 (46.51%), and 1003 (53.49%) were from Jaguapiru and Bororó villages, respectively. The median age of participants was 31 years, and 74.24% were females. Two individuals were detected with HTLV-1 . The phylogenetic analysis revealed that isolates belong to the Cosmopolitan subtype and the Transcontinental subgroup (HTLV-1aA). The low HTLV-1 prevalence found in this study is similar to that observed among blood donors, and pregnant populations from Mato Grosso do Sul. The absence of HTLV-2 infection among these Brazilian indigenous communities would suggest a distinct behavior pattern from other indigenous populations in Brazil. Lower socioeconomic and educational levels associated with cultural aspects of some ethnicities as cross-breastfeeding, polygamy, unprotected sex, and interaction with non-indigenous society, may expose them to risk factors that lead to an increase in the detection rate of infectious diseases6. Mato Grosso do Sul (MS), Central Brazil, is the second state with the largest indigenous population in Brazil7. The Guarani-Kaiowá, KiniKinawa, Kadiwéu, Terena, Guató, Atikum and Ofaié are the ethnicities present in the state8. This indigenous reserve, with about 18,000 people and located in Dourados city, 3474.50 ha, is represented mainly by the Guarani-Kaiowá and Terena ethnicities living in the Bororó and Jaguapiru villages10.The indigenous population in Brazil shows a high prevalence of sexually or vertically transmitted infections and a complex epidemiological profile12. It is estimated that 5–10 million people are infected by HTLV-1 worldwide. South Japan, sub-Saharan Africa, Caribbean islands, Melanesia, and South America are considered endemic regions for HTLV-1 infections13. HTLV-2 has no clinical manifestations well-defined and has been observed as prevalent in specific groups such as American indigenous populations and people who inject drugs (PWID)15. HTLV-1/2 are transmitted by sexual relations, transfusion/transplantation of contaminated blood/organs, and from mother to child, mainly by breastfeeding16.The Human T-lymphotropic virus 1 (HTLV-1) is a retrovirus associated with adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy (HAM), and other inflammatory diseases19. However, HTLV-1 infection can be found in this group in lower prevalence or in isolated cases20.HTLV-2 is predominant in the Brazilian indigenous population, which the prevalence can reach rates greater than 30%, mainly in the Kayapo Indigenous communities from the north of the countryOnce remaining gaps in the knowledge about HTLV infection in the country, especially among these indigenous people, this cross-sectional study aimed to investigate the prevalence, risk factors, and molecular characterization of HTLV among this second-largest indigenous reserve in Brazil located in Mato Grosso do Sul.The study population was conducted among indigenous individuals in Dourados City, MS, Central Brazil, from Bororó and Jaguapiru villages Fig. .Figure 1From September 2017 to March 2020, 2190 indigenous persons were invited, and 1875 agreed to participate in the study. Participants underwent an interview with a standardized questionnaire containing sociodemographic and sexual behavior information. Blood samples were collected from all subjects to perform serological tests. The inclusion criteria were being an indigenous community member from Bororó or Jaguapiru villages and aged over 18 years, unless unable to give informed written consent. All subjects gave their written informed consent to participate in the study. This study was approved by the Comissão Nacional de ética em Pesquisa (CONEP) under protocol number 2.000.496. All research was performed following relevant guidelines and regulations.All the serum samples were screened by an enzyme-linked immunosorbent assay (ELISA) commercial kit for the presence of anti-HTLV-1/2 antibodies (GOLD ELISA HTLV-I/II—REM), following the manufacturer’s instructions. Positive samples were repeatedly tested and confirmed by HTLV-1/2 Western Blot (WB) assay (MP Diagnostics HTLV BLOT 2.4–Singapore). HTLV infection was defined as a repeatedly positive ELISA and positive WB.21. Furthermore, the amplicons were purified using a QIA Quick Purification kit , according to the manufacturer’s instructions. The fragments were sequenced using BigDye Terminator Cycle Sequencing Ready Reaction Kit and ABI 3500XL  by Sanger’s method.The HTLV molecular characterization of ELISA and WB positive samples was performed by nested polymerase chain reaction (nested PCR). To this end, DNA was extracted from the whole blood of the anti-HTLV positive participants using the QIAamp DNA Blood mini kit (QIAgen), according to the manufacturer’s instructions. Then, the amplification of a 646 bp fragment of the HTLV-1 5’LTR region was performed by nested PCR as previously reportedThe HTLV-1 isolates were subjected to an analysis in the BLAST  after nucleotide sequencing to identify the subtype and subgroup. Nucleotide sequences were aligned and compared with 50 published HTLV-1 sequences available from GenBank with reference sequences used as outgroup, and sequences were searched with filter HTLV-1 and Transcontinental and Brazil using MAFFT v.7 (Multiple Alignment Program for Amino acid or nucleotide sequences). Phylogenetic analysis was performed using Maximum likelihood with 1000 bootstrap replicates with RAxML program and Bayesian method based on appropriate models determined by JModelTest (TIM2 + G model) with MR-base program on CYPRES Science Gateway. The phylogenetic tree was constructed by use of the FigTree v.1.4.4 program. The haplotype network was developed with NETWORK v.10.2 using the Median Joining algorithm.The GenBank nucleotide sequences accession number included in the phylogenetic analysis: Z32527, L02534, L76310, Y17014, KM023757, KM023765, D13784, AF033817, DQ235699, DQ235698, Y16481, AF054627, J02029, KY510690, KY510691, KY490575, KY490581, GQ443755-57, L36905, JF271836-38, JF271840-42, AY499185, AY920503, DQ471187-97, DQ70891-92, EU392159-60, FJ853490-91, OK247616-17, KM023763-62.The variables of interest were analyzed using STATA 13.0 software . Prevalence for serological markers of HTLV infection was estimated with 95% confidence intervals. Categorical variables were presented by absolute and percentage frequency. Continuous variables were expressed as mean, standard deviation, median, and range. The chi-square test was used to evaluate differences between proportions.The study involving human participants was reviewed and approved by the Comissão Nacional de Ética em Pesquisa (CONEP), an ethics Committee on Human Research, protocol number 2.000.496. The participants provided their written informed consent to participate in this study.A total of 1875 individuals were enrolled in the study. The median age of participants was 31 years, including 483 males (25.76%) and 1392 females (74.24%). Regarding the village, 872 (46.51%) and 1003 (53.49%) were from Jaguapiru and Bororó, respectively. Most of them declared belonging to Guarani-Kaiowá ethnicity (69.18%). In relation to formal education, 66.28% had more than 5 years of study.History of alcohol, drug, and sexually transmitted infections was reported by 27.68%, 3.73%, and 2.88% of the participants, respectively. None of them reported injectable drug use history. Other risk behaviors such as multiple sexual partners, irregular condom use, history of blood transfusion, tattoos, sharing sharp objects, and history of surgery are shown in Table Anti-HTLV was detected in two individuals . The two ELISA reactive samples were further tested by WB assay and confirmed anti-HTLV reactivity with complete profiles in the WB test for HTLV-1. The test results were subsequently referred to the health authorities responsible for this study population.The HTLV-1 5’LTR region was detected by nested PCR amplification in the two anti-HTLV-1 positive samples, which were successfully sequenced. The phylogenetic analysis revealed that both isolates were classified as belonging to the Cosmopolitan (1a) subtype and the Transcontinental (A) subgroup Fig. . The GenTable The other positive individual was an 81-year-old man (ID-137). Both individual ID-137 and ID-763 did not report any risk behaviors such as injection drug use, unprotected sexual intercourse, and multiple sexual partners. Both positive individuals were born in Dourados city, lived in Bororó village, and declared themselves Guarani-Kaiwá ethnicity.23. However, the results of this present study contrast with most of the studies conducted among indigenous populations in Brazil.This is the first investigation of HTLV-1/2 infection prevalence carried out among the indigenous population from Central Brazil. The prevalence of HTLV infection found in this study  is similar to the prevalence observed in the blood donors, and pregnant population from Mato Grosso do Sul 25. The high HTLV-2 prevalence in the indigenous population in Brazil usually differs between communities (from 1.4% in the Wayampi community on Amapá to 57.9% in the Kayapo community on Pará)26. Unlike these studies conducted in Brazil, the present study, no individuals infected with HTLV-2 were found.Several studies carried out among the indigenous population from the Brazilian Amazon region were developed, and HTLV-2 infection was shown to be prevalent, which is a change in the epidemiological pattern of this HTLV type in this specific group29. A prevalence study conducted among several Brazilian indigenous populations has already identified HTLV-1 infection, and all of them were from the North region of the country. Ishak et al.17 observed HTLV-1 infection prevalence of 2.94%, 0.67%, and 0.48% among Yanomami, Galibi, and Aukre communities, respectively. Besides, a prevalence of 0.62% was found in the Wayampi community in 2002, and one case was reported in the same community in 200730. The absence of more recent HTLV-1 studies in a Brazilian indigenous group may be due to the cultural characteristics of the studied communities since most studies are carried out in closed communities27. The geographic isolation of these villages limits contact with urban centers or other indigenous groups24. However, the Jaguapiru and Bororó villages are located 5 km from Dourados city, the second-largest city of Mato Grosso do Sul state, therefore geographically accessible to the urban center32. HTLV-1 infection was recently reported among Warao indigenous refugees living in urban area of Belém city33. Also, HTLV-1 is already reported in Indigenous people from other South American countries, such as Chile and Venezuela35. There was no difference of positivity for anti-HTLV  between female and male participants, respectively. These results are in accordance with studies conducted among the indigenous population in which no difference between genders was found36.The introduction of HTLV-1 in the Mato Grosso do Sul State probably occurred during the human migratory process from the slave trade from Africa and Japanese migration in the previous centuries23. The positive female individual (ID-763) reported that she was evaluated during her youngest daughter's pregnancy by the antenatal screening. She was diagnosed with positive anti-HTLV-1/2 and was recommended the interruption of breastfeeding since that time. The Brazilian Ministry of Health recommends the interruption of breastfeeding and the provision of milk formula substitutes feeding for those babies born from HTLV-1/2 seropositive mothers to avoid mother-to-child transmission16. Although these measures, adequate counseling with information about HTLV-1 transmission or clinical evaluation to identify signs or symptoms of HTLV-1 associated diseases was not offered to the ID-763 participant. This demonstrates the need to spread knowledge about HTLV infection and the public health policies that are already implemented in Brazil to properly provide counseling for positive patients.HTLV-1 testing has been included in the routine antenatal screening of the state of Mato Grosso do Sul by the Program for Protection of Pregnant Woman since 2002The HTLV-1aA sequences present in this study diverge from the previous studies conducted in Brazil among indigenous populations that found mainly HTLV-2. The sequences obtained from the present study grouped next with other isolates from various non-indigenous populations and geographical regions in Brazil, such as people who use drugs, Afro-descendants, pregnant women, blood donors, and people who live with HIV (PLHIV), suggesting a possible HTLV-1 transmission from these non-indigenous individuals. Unfortunately, sequences from other worldwide indigenous populations belonging to the Transcontinental subgroup (HTLV-1aA) were not found registered on Genbank.Some limitations must be acknowledged. First, underreporting of risk behaviors and reporting bias are some of the limitations of this cross-sectional study. Because some of them may have been omitted during the interviews due to the distrust of discrimination and stigma. In addition, individuals from the micro-areas of indigenous health care were enrolled by convenience sampling, with greater acceptance of the study among residents of the Bororó village, resulting in unequal sample distribution between them. Because of the low number of HTLV infected individuals in this study, regression analysis could not be performed. Despite these limitations, this study is representative of the indigenous population of Central Brazil since we used a large sample size. Moreover, our study has important information which would contribute to closing the gaps in HTLV epidemiology and controlling public policies.37. Also, the absence of HTLV-2 infection among these Brazilian indigenous communities would suggest a behavior pattern distinct from other indigenous populations in Brazil.The results of the study show the presence and circulation of HTLV-1 in indigenous populations from Jaguapiru and Bororó villages in Dourados City, MS. A better understanding of the patterns of occurrence of HTLV-1 in the indigenous population of Mato Grosso do Sul is critical to guiding the development of public health initiatives to reduce transmission. Although a higher risk of infection has been supposed for this specific study population, the prevalence rate of HTLV-1 infection found in this study was similar to that observed among Brazilian blood donors (0.48%)Supplementary Figure S1.


This study aimed to compare the survival outcome of 3 different treatment groups  for locally advanced cervical cancer.A total of 187 patients with pathological stage IB3–IIB cervical cancer  hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019 were included. Therefore, this article is a retrospective study. We collected data from all eligible patients. And all according to the treatment methods at that time, they were divided into three subgroups: (1) 40 patients who received neoadjuvant arterial interventional chemotherapy + surgery + postoperative chemotherapy (IA-NAC + RS), (2) 63 patients who received neoadjuvant intravenous chemotherapy + surgery + postoperative chemotherapy (IV-NAC + RS), (3) 84 patients who only received concurrent chemoradiotherapy (CCRT). Notably, 108 of these patients met the 5-year follow-up period, and 187 patients met the 3-year follow-up period only. Consequently, we compared 5-year survival and 3-year survival separately. The prognosis  of the three groups and the chemotherapy efficacy, intraoperative blood loss, operation time, and postoperative pathological risk factors of different subgroups were compared.p > 0.05). (2) The chemotherapy response rates of IA-NAC+RS group (37.5%) and IV-NAC+RS group (25.4%) were comparable (p > 0.05). (3) The intraoperative blood loss in the IA-NAC+RS group (average 92.13±84.09 mL) was significantly lower than that in the IV-NAC+RS group (average 127.2±82.36 mL) (p < 0.05). (4) The operation time of the IA-NAC+RS group (average 231.43±63.10 min) and the IV-NAC+RS group (average 219.82±49.11 min) were comparable (p > 0.05). (5) There were no significant differences between the IA-NAC+RS group and IV-NAC+RS group in pathological lymph node metastasis, parametrial invasion, and involvement of lymphovascular space (p > 0.05).(1) There were no significant differences in the 3-year overall survival (OS) rate, 3-year progression-free survival (PFS) rate, 5-year OS rate, and 5-year PFS rate among the three subgroups (Neoadjuvant chemotherapy combined with surgery had the same long-term survival benefit as concurrent chemoradiotherapy. The incidence rates of cervical cancer are only to that of breast cancer worldwide, and the leading cause of cancer deaths among women in developing countries . In ChinThe concurrent chemoradiotherapy (CCRT) is recommended as the primary treatment for locally advanced cervical cancer (LACC) in the 2022 NCCN guidelines . HoweverPreoperative arterial chemotherapy for locally advanced cervical cancer can be traced back as far as the 1960s. The first report on IA-NAC was published in 1950 by Bierman et al. , and itsThis study mainly aimed to compare the long-term outcomes of different subgroups receiving neoadjuvant arterial interventional chemotherapy + surgery + chemotherapy (IA-NAC+RS), neoadjuvant intravenous chemotherapy + surgery + chemotherapy (IV-NAC+RS), or CCRT in a retrospective study of LACC. These results may provide guidance for clinicians to choose therapeutic methods of LACC.At the beginning of the study, we included a total of about 300 patients who were diagnosed as LACC in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019. However, some patients were subsequently excluded from the group because they did not meet the inclusion and exclusion criteria or there was a serious lack of information. And finally, we included 187 patients who met the requirements. Patients in the NACT subgroup did not receive radiation therapy after the follow-up study. Some patients did not need radiotherapy based on postoperative pathological evaluation, and some patients refused radiotherapy for personal reasons.The inclusion criteria are as follows: (1) clinical stage (FIGO 2018) IB3-IIB and lesion diameter ≥4cm and (2) squamous cell carcinoma, adenosquamous carcinoma, and adenocarcinoma. The exclusion criteria are as follows: (1) the presence of contraindications to radiotherapy and chemotherapy such as abnormal liver, kidney, and bone marrow function; (2) history of tumors; (3) the NACT (IA-NAC+RS and IV-NAC+RS) group received radiotherapy; (4) pregnancy, heart disease, and other comorbidities.This study was a retrospective study. We selected patients between January 2013 and May 2019. Among this group of patients, we selected the appropriate patients for enrollment based on the inclusion criteria. Then collect relevant information , and the allocation of patients was based on the discretion of the treating physicians at that time. The patients were divided into 3 subgroups according to the treatments: 40 patients who received IA-NAC+RS, 63 patients who received IV-NAC+RS, and 84 patients who received CCRT. The demographic characteristics  were similar in these three subgroups. This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.2) was injected into the uterine artery, and gelatin sponge particles were used to embolize the anterior trunk of the internal iliac artery. Repeated angiography was successful when the blood flow of the target artery disappeared. After the operation, the catheter was extubated. After treatment, the catheters were removed, and sandbags were placed to apply firm pressure to the groin for 6 h. Hydration with normal saline and 5% dextrose was started from 3h before IA-NAC and was continued to maintain a urine output >100 ml/h for 24 h.All patients received 1–2 times arterial interventional chemotherapy (paclitaxel combined with platinum), then underwent laparoscopic radical hysterectomy + pelvic lymph node dissection, and received 2–5 times postoperative chemotherapy (paclitaxel combined with platinum). The times of NACT depended on the patient’s tolerance and clinical response. The specific operation of arterial interventional chemotherapy was as follows. Under the surveillance of digital subtraction angiography, the right femoral artery was punctured using the Seldinger technique. Cobra catheters were introduced for cannulation and angiography of bilateral internal iliac arteries and uterine arteries, respectively. Diluted platinum . The interval between each chemotherapy treatment is 3–4 weeks. The entire pelvis was externally irradiated (1.8 or 2 Gy) 23 to 25 times, totaling 45 to 50 Gy, according to Radiation Therapy Oncology Group guidelines. Brachytherapy was given at point A with the high dose rate (HDR) of 6 Gy per session for a total of 5 sessions (once a week).2. Platinum included cisplatin (30–40 mg/m2) and loplatin (30–40 mg/m2).All patients received 1–2 times neoadjuvant intravenous chemotherapy (paclitaxel combined with platinum), then followed by laparoscopic radical hysterectomy + pelvic lymph node dissection, and 2–5 times of paclitaxel combined with platinum chemotherapy after operation. The times of neoadjuvant chemotherapy depended on the patient’s tolerance and clinical response. During the treatment, patients were treated with paclitaxel combined with platinum. Of these, paclitaxel was 135–175 mg/mPatients on neoadjuvant chemotherapy were evaluated for status before the next chemotherapy, and some patients responded well enough to undergo surgery directly after 1 chemotherapy session. For patients with lesion reduction after neoadjuvant chemotherapy, chemotherapy could be continued another neoadjuvant chemotherapy. In our study, 29 people in the IA-NAC+RS group had only 1 neoadjuvant chemotherapy and 46 people in the IV-NAC+RS group had only 1 neoadjuvant chemotherapy.This fraction of patients treated with neoadjuvant chemotherapy was treated with 3–5 more sessions of chemotherapy (paclitaxel combined with platinum) after surgery. The interval between each chemotherapy treatment is 3–4 weeks. In principle, radiotherapy should be added to patients with pelvic lymph node metastasis, cervical myometrial invasion greater than 1/2, tumor thrombus in vessels, and parametrial cancer invasion. In this article, patients with high-risk positive postoperative pathology have communicated with the patients and their families, who refused radiotherapy for personal reasons.In this study, the method of direct observation and measurement of tumor lesion size was adopted, and some patients were evaluated concerning vaginal ultrasound or CT or MRI. Tumor response to NACT and chemoradiation was assessed according to the World Health Organization criteria . CompletAfter completion of the entire treatment, all patients were evaluated every 3 months for the first 2 years and every 6 months from 2 to 5 years. Inspections during follow-up included pelvic MRI, urinary ultrasound and liver and kidney ultrasound, cervical smear, X-ray, and tumor markers. The primary endpoints of the study included 5-year progression-free survival (PFS) and 5-year OS, and secondary endpoints included 3-year PFS and 3-year OS. PFS was the time from the date of treatment to tumor recurrence or the last follow-up time; OS was the time from the day of treatment to death or last follow-up.χ2 test, continuous corrected chis-square test, or Fisher’s test. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. And p<0.05 was considered statistically significant.We used SPSS 26.0 for the statistical analysis. Quantitative data were expressed as mean ± standard deviation after the normality test which obeyed normal distribution, and non-normal distribution was expressed as a median. Qualitative data were compared using the p > 0.05).A total of 187 eligible patients were included in the study. The baseline characteristics of the included patients are shown in Table χ2 test was used to compare the pathological characteristics that may affect the prognosis, and it was found that there were no significant differences in lymph node metastasis, positive incision margin, and lymphovascular space involvement between the two subgroups , which were 92.5%, 90.5%, and 89.3% respectively. There were also no significant differences in the three subgroups regarding 3-year OS rates (p = 0.816), which were 97.5%, 95.2%, and 95.2% respectively  , which were 93.9%, 92.7%, and 89.3%. The 3-year OS rates of these three subgroups were 97.0%, 98.2%, and 95.2%, and the differences were also not statistically significant (p = 0.64)  , both with abnormally high swelling markers. Two patients in the IV-NAC+ RS group died during the 3-year follow-up period and two patients died during the 5-year follow-up period. Among the patients in the CCRT group, 12 patients relapsed (9 patients relapsed during the 3-year follow-up period) and 6 patients died of relapse.p > 0.05), but there was a significant difference in the amount of blood loss between the two subgroups (p<0.05).All patients underwent radical hysterectomy + pelvic lymphadenectomy (+ oophorectomy or ovarian transposition). The operative time in the IA-NAC+RS group was 120–460 min, and the mean time was 231.43±63.10 min. Intraoperative bleeding of this group was 20–400 mL, with an average of 92.13±84.09 mL. The operation time of the IV-NAC+RS group was 130–311min, and the average time was 219.82±49.11min. Intraoperative bleeding was 20–300 mL, with an average of 127.2±82.36 ml. There was no significant difference in operation time between these two subgroups  was comparable to that of IV-NAC+ RS group (25.4%), and the difference was not statistically significant , and the difference was statistically significant . But the operation time in the IA-NAC+RS group was slightly higher than that one. Considering that the tissue was in a state of congestion during the operation after interventional chemotherapy, it was related to the fibrosis of the parametrial tissue caused by embolization.The approaches of neoadjuvant chemotherapy include arterial interventional chemotherapy and intravenous chemotherapy. In this study, arterial interventional chemotherapy was superior to intravenous chemotherapy in terms of surgery and long-term benefits. As for surgery, the intraoperative blood loss in the IA-NAC+RS group was less than that in the IV-NAC+RS group. This is mainly because preoperative arterial chemotherapy can better achieve the purpose of tumor shrinkage and blood supply reduction . The opep > 0.05, Table In addition, we also compared the pathological features that may affect the prognosis and found that there was no significant difference between the two groups (IA-NAC+RS group versus IV-NAC+RS group) in lymph node metastasis, positive resection margin, and lympho-vascular space involvement  has the same survival benefit compared with CCRT. At the same time, based on the same survival benefit of interventional arterial chemotherapy and intravenous chemotherapy, interventional arterial chemotherapy can achieve better surgical. For limited included patients in our retrospective study, the above conclusions should be drawn cautiously. The choice of treatment for LACC needs to be further explored through a prospective randomized controlled study.